Nevin Manimala

JMIR Form Res. 2022 Nov 4;6(11):e38164. doi: 10.2196/38164.

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) infection is the most common sexually transmitted infection in the United States. High-risk HPV strains are associated with cancer of the cervix, oropharynx, anus, rectum, penis, vagina, and vulva. To combat increasing HPV-related cancers, the 9-valent HPV vaccine Gardasil was developed. Recommendation of the HPV vaccine by a health care provider has been cited as the number one factor affecting vaccine uptake among adolescents and young adults. Physician assistants, nurse practitioners, and pharmacists have been enlisted to bridge the gap.

OBJECTIVE: The specific aim of this research study was to develop a reliable and valid HPV vaccine communication scale that can be used to measure the competency of primary care providers when recommending the need for vaccination to parents and patients.

METHODS: Using a descriptive study, we collected data via a literature review, focus groups, and an expert panel to inform the scale domains and blueprint design. Pretesting (cognitive interviews) was used to inform item revision decisions. An item analysis was also conducted for the responses provided in the cognitive interviews. Item statistics (means and SDs), interitem correlations, and reliability were examined. Data were analyzed using SPSS (IBM Corp) software.

RESULTS: A valid and reliable 42-item HPV vaccine communication competency scale was developed. The scale included 6 domains of interest. Scale items were moderately to strongly correlated with one another, and Cronbach α indicated good internal consistency with each scale. Scale items included were related to provider introduction or rapport (α=.796), patient respect or empathy (α=.737), provider interview or intake (α=.9), patient counseling or education (α=.935), provider communication closure (α=.896), and provider knowledge (α=.824).

CONCLUSIONS: Pharmacists, nurse practitioners, and physician assistants should be trained to be competent in HPV vaccine communication and recommendation due to their expanded roles. Interdisciplinary collaboration is important to account for the trainee’s individual differences and ensure the best health care outcomes for patients. A standardized HPV communication scale can be used to ensure effective and consistent recommendation by health care providers, thus affecting immunization rates.

PMID:36331545 | DOI:10.2196/38164

JMIR Mhealth Uhealth. 2022 Nov 4;10(11):e38951. doi: 10.2196/38951.

ABSTRACT

BACKGROUND: Barriers to accessing in-person care can prevent veterans with posttraumatic stress disorder (PTSD) from receiving trauma-focused treatments such as exposure therapy. Mobile apps may help to address unmet need for services by offering tools for users to self-manage PTSD symptoms. Renew is a mobile mental health app that focuses on exposure therapy and incorporates a social support function designed to promote user engagement.

OBJECTIVE: We examined the preliminary efficacy of Renew with and without support from a research staff member compared with waitlist among 93 veterans with clinically significant PTSD symptoms. We also examined the impact of study staff support on participant engagement with the app.

METHODS: In a pilot randomized controlled trial, we compared Renew with and without support from a research staff member (active use condition) with waitlist (delayed use condition) over 6 weeks. Participants were recruited through online advertisements. The Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) was used to measure PTSD symptoms at pre, post, and 6-week follow-up. Usage data were collected to assess engagement with Renew.

RESULTS: Results indicated a small effect size (d=-0.39) favoring those in the active use conditions relative to the delayed use condition, but the between-group difference was not significant (P=.29). There were no differences on indices of app engagement between the 2 active use conditions. Exploratory analyses found that the number of support persons users added to the app, but not the number of support messages received, was positively correlated with app engagement.

CONCLUSIONS: Findings suggest Renew may hold promise as a self-management tool to reduce PTSD symptoms in veterans. Involving friends and family in mobile mental health apps may help bolster engagement with no additional cost to public health systems.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04155736; https://clinicaltrials.gov/ct2/show/NCT04155736.

PMID:36331540 | DOI:10.2196/38951

J Med Internet Res. 2022 Nov 4;24(11):e39728. doi: 10.2196/39728.

ABSTRACT

BACKGROUND: Virtual care (VC) visits (telephone or video) and email-based patient communication have been rapidly adopted to facilitate cancer care during the COVID-19 pandemic. Inequities in access and patient experience may arise as these digital health tools become prevalent.

OBJECTIVE: We aimed to characterize inequities in access and patient-reported experience following adoption of digital health tools at a tertiary cancer center during the COVID-19 pandemic.

METHODS: We designed a cross-sectional study of outpatients with visits from September to December 2020. Patient characteristics and responses to an email-based patient-experience survey were collated. Inequities in access were assessed across three pairs of comparison groups: (1) patients with VC and in-person visits, (2) patients with and without documented email addresses, and (3) responders and nonresponders to the survey. Inequities in patient-reported experience were assessed among survey responders. Demographics were mapped to area-level averages from national census data. Socioeconomic status was mapped to area-level dimensions of the Canadian Index of Multiple Deprivation. Covariate balance between comparison groups was assessed using standardized mean differences (SMDs), with SMD≥0.2 indicating differences between groups. Associations between patient experience satisfaction scores and covariates were assessed using multivariable analyses, with P<.05 indicating statistical significance.

RESULTS: Among the 42,194 patients who had outpatient visits, 62.65% (n=26,435) had at least one VC visit and 31.15% (n=13,144) were emailable. Access to VC and email was similar across demographic and socioeconomic indices (SMD<0.2). Among emailable patients, 21.84% (2870/13,144) responded to the survey. Survey responsiveness was similar across indices, aside from a small difference by age (SMD=0.24). Among responders, 24.4% received VC and were similar to in-person responders across indices (SMD<0.2). VC and in-person responders had similar satisfaction levels with all care domains surveyed (all P>.05). Regardless of visit type, patients had variable satisfaction with care domains across demographic and socioeconomic indices. Patients with higher ethnocultural composition scores were less satisfied with the cultural appropriateness of their care (odds ratio [OR] 0.70, 95% CI 0.57-0.86). Patients with higher situational vulnerability scores were less satisfied with discussion of physical symptoms (OR 0.67, 95% CI 0.48-0.93). Patients with higher residential instability scores were less satisfied with discussion of both physical (OR 0.81, 95% CI 0.68-0.97) and emotional (OR 0.86, 95% CI 0.77-0.96) symptoms, and also with the duration of their visit (OR 0.85, 95% CI 0.74-0.98; P=.02). Male patients were more satisfied with how their health care provider had listened to them (OR 1.64, 95% CI 1.11-2.44; P=.01).

CONCLUSIONS: Adoption of VC and email can equitably maintain access and patient-reported experience in cancer care across demographics and socioeconomic indices. Existing health inequities among structurally marginalized patients must continue to be addressed to improve their care experience.

PMID:36331536 | DOI:10.2196/39728

J Obstet Gynaecol. 2022 Nov 4:1-4. doi: 10.1080/01443615.2022.2141618. Online ahead of print.

ABSTRACT

This study aims to clarify the effect of postmenopausal bilateral oophorectomy on plasma steroid hormone levels. Women who were submitted in the postmenopausal period to hysterectomy for uterine benign conditions were divided into two groups: 18 women had isolated hysterectomy and 11 had hysterectomy with bilateral salpingo-oophorectomy. In both groups serum hormone levels were quantified by solid phase extraction and gas chromatography and tandem mass spectrometry. Differences in dehydroepiandrosterone (DHEA), testosterone, androstenedione and oestradiol were determined in both groups. The analysis revealed lower steroid levels in the bilateral salpingo-oophorectomy group when compared to the isolated hysterectomy group with statistically significant differences found for DHEA (5.8 ± 3.2 vs. 9.4 ± 4.4 ng/mL; p = 0.019) and oestradiol (0.69 ± 0.4 vs. 1.48 ± 4.3 ng/mL; p = 0.007). The results are consistent with a significant endocrine activity of the postmenopausal ovary. The clinical consequences of these findings need to be clarified and postmenopausal prophylactic bilateral salpingo-oophorectomy re-evaluated.IMPACT STATEMENTWhat is already known on this subject? Although it is consensual that premenopausal prophylactic bilateral oophorectomy should not be performed because it has harmful effects on women’s health, the evidence regarding the effects of postmenopausal prophylactic bilateral oophorectomy is scarce and this procedure continues to be a regular practice. Few studies have demonstrated that postmenopausal ovaries still have endocrine activity that may impact older women’s health.What do the results of this study add? This is the first study to compare hormone levels of postmenopausal women based on their hysterectomy and oophorectomy status using GC-MS/MS, a highly sensitive bioanalytical assay for the measurement of steroid hormones. Previous studies relied on immunoassays and did not compare DHEA levels, which according to the intracrinology theory is a precursor for androgens and oestrogens. In this study, statistically significant lower levels of DHEA and oestradiol were found after postmenopausal bilateral salpingo-oophorectomy.What are the implications of these findings for clinical practice and/or further research? This is a pilot study that may lead to further investigation in this area to clarify the impact of the prophylactic removal of postmenopausal ovaries on older women’s health and lead to changes in surgical procedures.

PMID:36331514 | DOI:10.1080/01443615.2022.2141618

JAMA Netw Open. 2022 Nov 1;5(11):e2240383. doi: 10.1001/jamanetworkopen.2022.40383.

ABSTRACT

IMPORTANCE: There is no consensus on interventions to slow the progress of hip displacement in patients with cerebral palsy.

OBJECTIVE: To investigate the efficacy of a novel hip brace in preventing progressive hip displacement in patients with cerebral palsy.

DESIGN, SETTING, AND PARTICIPANTS: This 2-group randomized clinical trial was conducted at 4 tertiary hospitals in South Korea from July 2019 to November 2021. Participants included children aged 1 to 10 years with nonambulatory cerebral palsy (Gross Motor Function Classification System level IV or V). Block randomization was used to assign an equal number of patients to the study and control groups via computerized random allocation sequences. Data were analyzed from November to December 2021.

INTERVENTIONS: The intervention group wore the hip brace for at least 12 hours a day for the study duration (ie, 12 months). Follow-up evaluations were performed after 6 and 12 months of wearing the brace. Both groups proceeded with conventional rehabilitation therapy during the trial.

MAIN OUTCOMES AND MEASURES: The primary outcome was the Reimers migration index (MI) on radiography, as assessed by 3 blinded investigators. Primary outcome variables were analyzed using linear mixed models. Secondary outcomes include change in the Caregiver Priorities & Child Health Index of Life with Disabilities, on which lower scores indicate better quality of life.

RESULTS: A total of 66 patients were included, with 33 patients (mean [SD] age, 68.7 [31.6] months; 25 [75.8%] boys) randomized to the intervention group and 33 patients (mean [SD] age, 60.7 [24.9] months; 20 [60.6%] boys) randomized to the control group. The baseline mean (SD) MI was 37.4% (19.3%) in the intervention group and 30.6% (16.3%) in the control group. The mean difference of the MI between the intervention group and control group was -8.7 (95% CI, -10.2 to -7.1) percentage points at 6 months and -12.7 (95% CI, -14.7 to -10.7) percentage points at 12 months. The changes in the Caregiver Priorities & Child Health Index of Life with Disabilities were favorable in the study group and reached statistical significance at the 6-month follow-up compared with the control group (difference, -14.2; 95% CI, -25.2 to -3.3).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the novel hip brace was significantly effective in preventing the progression of hip displacement, compared with the control group. It effectively improved quality of life in patients with nonambulatory cerebral palsy. Therefore, hip brace use could be a promising treatment method to delay hip surgery and improve the quality of life of patients with nonambulatory cerebral palsy.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04033289.

PMID:36331502 | DOI:10.1001/jamanetworkopen.2022.40383

Hum Reprod. 2022 Nov 4:deac234. doi: 10.1093/humrep/deac234. Online ahead of print.

ABSTRACT

STUDY QUESTION: Are maternal urinary isoflavone (ISO) concentrations during pregnancy associated with anogenital distance (AGD) in infants at birth, and at 6 and 12 months of age?

SUMMARY ANSWER: Higher maternal urinary ISO concentrations during pregnancy were associated with longer AGD in infants of both sexes, and equol (EQU) and daidzein (DAD) were identified as the important ISO mixture components in the observed associations.

WHAT IS KNOWN ALREADY: Evidence of the association of prenatal exposure to ISO with offspring’s AGD is mainly derived from animal studies, which used different study designs and had inconsistent results. Only one human study has been reported and it found null associations between maternal ISO exposure during pregnancy and AGD among boys at birth, with a small sample size and a wide range of exposure windows. No human study on girls was found.

STUDY DESIGN, SIZE, DURATION: Prospective cohort study (Shanghai-Minhang Birth Cohort Study), with pregnant women recruited at 12-16 weeks of gestation in Shanghai, China between April and December 2012. One thousand two hundred and twenty-five live singletons were left in the cohort at delivery of which 480 mother-infant pairs had data on both maternal urinary ISO concentrations and at least one AGD measurement and were included in the present study. Anopenile distance (AGDAP) and anoscrotal distance (AGDAS) of boys and anoclitoral distance (AGDAC) and anofourchette distance (AGDAF) of girls were measured at birth and at 6 and 12 months of age.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Multiple linear regression models were used to examine the associations between maternal ISO concentrations and AGD. Bayesian kernel machine regression (BKMR) was implemented to examine both the overall effects of ISO mixture and the single effect of each ISO and identify important components of ISO mixture.

MAIN RESULTS AND THE ROLE OF CHANCE: A general profile of higher concentrations of maternal ISO associated with longer AGD in infants of both sexes was observed, when maternal education, parity, BMI before pregnancy (BMI, categorical variable), passive smoking during early pregnancy, age at delivery, gestational weeks and infant body size were adjusted for. Among boys, EQU was associated with increased AGDAS at birth and at 6 and 12 months, and DAD was associated with increased AGDAP at birth. Among girls, the associations of EQU and DAD with increased AGDAC and AGDAF at birth were found. When gestational weight gain and feeding patterns of infants in the first 6 months were additionally adjusted for, and maternal BMI was adjusted for as a continuous variable, more pronounced associations were observed, especially for associations of genistein (GEN), DAD and glycitein (GLY) with increased AGDAP and AGDAS at 6 months in boys. However, these associations were not always observed in the highest tertile group, and no consistent dose-response relationships were found. Similar results were observed in BKMR models, showing positive correlations of concentration of ISO mixture with increased AGDAS at both 6 and 12 months among boys, and increased AGDAC and AGDAF at birth among girls. Statistically significant increments of 4.96 mm (95% credible interval (CrI): 1.40, 8.52) and 1.07 mm (95% CrI: 0.02, 2.13) in AGDAS at 6 months among boys and AGDAC at birth among girls, respectively, were observed at the 75th percentile of ISO mixture, compared with 25th percentile. EQU and DAD were identified as the important components among ISO-AGD associations.

LIMITATIONS, REASONS FOR CAUTION: First, due to the short half-lives of ISO, the accuracy of a single spot urine sample reflecting ISO exposure during pregnancy may be limited, and thus may cause non-differential misclassification. Second, despite the adjustments for several important covariates in the study, unmeasured and residual confounding factors may remain a concern. Third, false discovery due to multiple testing may remain. Finally, the reduced sample sizes attributed to the loss of follow-up and missing data of confounders may limit our ability to detect an association, if any existed.

WIDER IMPLICATIONS OF THE FINDINGS: Prenatal ISO exposure may affect the reproductive development of offspring. As ISO can be widely detected in pregnant women, especially in Eastern countries, more studies are warranted to provide evidence of the effects of prenatal ISO exposure on long-term reproductive outcomes.

STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Key Research and Development Program of China (2021YFC2701003), the National Natural Science Foundation of China (22076123), the Science and Technology Commission of Shanghai Municipality (21ZR1454700 and 20ZR1448000), the Shanghai Municipal Health Commission (20194Y0160) and Innovation-oriented Science and Technology Grant from NHC Key Laboratory of Reproduction Regulation (CX2022-04). The authors have no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER: N/A.

PMID:36331496 | DOI:10.1093/humrep/deac234

Rheumatology (Oxford). 2022 Nov 4:keac626. doi: 10.1093/rheumatology/keac626. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the present study was to detect preclinical changes in SLE patients in retinal microvascularization or retinal and optical nerve structure by optical coherence tomography.

METHODS: This cross-sectional, single-center study aimed to describe structural changes (macular and retinal nerve fiber layer [RNFL] thickness) by structural spectral-domain optical coherence tomography (SD-OCT) and perifoveal vascular (vascular density [VD] and perfusion [VP] and foveal avascular zone [FAZ] structural parameters) findings by OCT-angiography (OCTA) in 78 SLE patients and 80 healthy volunteers. In addition, we analyzed their association with clinical and laboratory parameters, medications received, disease duration and SLE activity and damage.

RESULTS: Structural parameters by SD-OCT and perifoveal vascular parameters by OCTA were decreased in SLE patients compared with controls. OCTA parameters (VD, VP and FAZ circularity) and macular thickness were also decreased in patients with longer disease duration (>10 years). The presence of antiphospholipid antibodies was associated with a decreased RNFL thickness, mainly in the inferior quadrants. Patients developing antiphospholipid syndrome also showed decreased RNFL thickness and OCTA flow changes. SD-OCT and OCTA results were not associated with disease activity. Foveal structural parameters were lower in patients with higher damage score.

CONCLUSION: SD-OCT and OCTA can detect preclinical structural and microcirculatory changes in SLE patients. Structural and perifoveal vascular macular changes in SLE patients are related with disease duration. Macular structural parameters were impaired in patients with higher disease damage. Antiphospholipid syndrome seems to be associated with preclinical damage of the optic nerve and impairment of the perifoveal microvasculature.

PMID:36331348 | DOI:10.1093/rheumatology/keac626

Cancer Commun (Lond). 2022 Nov 4. doi: 10.1002/cac2.12383. Online ahead of print.

ABSTRACT

BACKGROUND: Although programmed cell death 1 (PD-1) blockade plus chemotherapy can significantly prolong the progression-free survival (PFS) and overall survival (OS) in first-line settings in patients with driver-negative advanced non-small-cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy.

METHODS: Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations.

RESULTS: Responders had significantly higher CD8/PD-L1 (P = 0.015) or CD68/PD-L1 co-expression levels (P = 0.021) than non-responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co-expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co-expression subgroups. The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression, the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD-L1 co-expression group.

CONCLUSION: Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.

PMID:36331328 | DOI:10.1002/cac2.12383

Eur Heart J. 2022 Nov 4:ehac594. doi: 10.1093/eurheartj/ehac594. Online ahead of print.

ABSTRACT

BACKGROUND: Inclisiran, an siRNA administered twice-yearly, significantly reduced LDL cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a lower risk of cardiovascular (CV) events is not yet established.

METHODS AND RESULTS: Patient-level, pooled analysis of ORION-9, -10 and -11, included patients with heterozygous familial hypercholesterolaemia, atherosclerotic CV disease (ASCVD), or ASCVD risk equivalent on maximally tolerated statin-therapy, randomized 1:1 to receive 284 mg inclisiran or placebo on Days 1, 90, and 6-monthly thereafter for 18 months. Prespecified exploratory endpoint of major cardiovascular events (MACEs) included non-adjudicated CV death, cardiac arrest, non-fatal myocardial infarction (MI), and fatal and non-fatal stroke, evaluated as part of safety assessments using a standard Medical Dictionary for Regulatory Activities basket. Although not prespecified, total fatal and non-fatal MI, and stroke were also evaluated. Mean LDL-C at baseline was 2.88 mmol/L. At Day 90, the placebo-corrected percentage reduction in LDL-C with inclisiran was 50.6%, corresponding to an absolute reduction of 1.37 mmol/L (both P < 0.0001). Among 3655 patients over 18 months, 303 (8.3%) experienced MACE, including 74 (2.0%) fatal and non-fatal MIs, and 28 (0.8%) fatal and non-fatal strokes. Inclisiran significantly reduced composite MACE [OR (95% CI): 0.74 (0.58-0.94)], but not fatal and non-fatal MIs [OR (95% CI): 0.80 (0.50-1.27)] or fatal and non-fatal stroke [OR (95% CI): 0.86 (0.41-1.81)].

CONCLUSION: This analysis offers early insights into the potential CV benefits of lowering LDL-C with inclisiran and suggests potential benefits for MACE reduction. These findings await confirmation in the larger CV outcomes trials of longer duration.

PMID:36331326 | DOI:10.1093/eurheartj/ehac594

Eur Heart J. 2022 Nov 4:ehac615. doi: 10.1093/eurheartj/ehac615. Online ahead of print.

ABSTRACT

AIMS: Patients often require combination therapies to achieve LDL cholesterol (LDL-C) targets for the primary prevention of atherosclerotic cardiovascular disease. This study investigates the effect of inclisiran, a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 production, in primary prevention patients with elevated LDL-C despite statins.

METHODS AND RESULTS: This pre-specified analysis of the placebo-controlled, randomized ORION-11 trial included 203 individuals at risk of, but without prior, cardiovascular events and LDL-C ≥2.6 mmol/L, despite maximally tolerated statins. Inclisiran 284 mg or placebo was administered on Days 1, 90, and thereafter every 6 months up to 540 days. Co-primary endpoints were percentage LDL-C change from baseline to Day 510 and time-adjusted change from baseline after Day 90 and up to Day 540. Key secondary endpoints included percentage and absolute changes in atherogenic lipoproteins. Safety was assessed over 540 days. The mean baseline (SD) LDL-C was 3.6 (1.5) mmol/L. At Day 510, the placebo-corrected LDL-C change with inclisiran was -43.7% [95% confidence interval (CI): -52.8 to -34.6] with a corresponding time-adjusted change of -41.0% (95% CI: -47.8 to -34.2); (P < 0.0001). The placebo-corrected absolute change in LDL-C at Day 510 with inclisiran was -1.5 mmol/L (95% CI: -1.8 to -1.2), with a respective time-adjusted change of -1.3 mmol/L (95% CI: -1.6 to -1.1). Inclisiran significantly lowered non-HDL cholesterol and apolipoprotein B (apoB) at Day 510 vs. placebo (P < 0.0001 for both), with a greater likelihood of attaining lipoprotein and apoB goals, and was well-tolerated except for mainly mild, treatment-emergent adverse events at the injection site.

CONCLUSION: Inclisiran was generally well-tolerated in primary prevention patients with elevated LDL-C, who derived significant reductions in atherogenic lipoprotein levels with twice-yearly maintenance dosing.

PMID:36331315 | DOI:10.1093/eurheartj/ehac615